For the treatment of severe hemorrhage, there is no ideal blood substitute, which sustains the circulation and provides tissue oxygenation. The long-term objective of this research project is to determine whether glutaraldehyde-stabilized bovine stroma-free hemoglobin solution (SB-SFHS) might serve in that capacity. The premise to the proposed work is represented by the demonstrated similarity of molecular structure between bovine and human hemoglobins, the higher P50 value of bovine as compared to human hemoglobin, the lack of immunogenicity of bovine SFHS in single large volume infusions, the ability of SB-SFHS to sustain life in the rabbit following acute hemorrhage representing 66% of blood volume and the ability of SB-SFHS to resuscitate dogs subjected to hemorrhagic shock (preliminary experiments). In addition, bovine hemoglobin is in rich supply. The specific aim of this proposal is to determine the efficacy of SB-SFHS as resuscitative fluid for the treatment of hemorrhagic shock. Three groups of dogs will be subjected to a Wiggers' shock preparation and respectively treated with whole blood, plasma protein fraction (PPF), or SB-SFHS. The three forms of treatment will be compared by studying their respective effects upon both hemo- and oxygen-dynamics. Attention will be focused on mixed venous blood oxygen tension and its main determinants (cardiac output, hemoglobin concentration - both intra- and extra-cellular-, hemoglobin oxygen affinity, oxygen transport and delivery). The contribution of SB-SFHS to oxygen transport will be evaluated by measuring the oxygen content of arterial and mixed venous plasma, separately from that of the red blood cells. The effects of SB-SFHS as resuscitative fluid are expected to be better than those of PPF. Should this efficacy be demonstrated, further studies are contemplated for an analysis of toxicity and immunogenicity.